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Frontiers in Immunology 2022Influenza A virus (IAV) is widely disseminated across different species and can cause recurrent epidemics and severe pandemics in humans. During infection, IAV attaches... (Review)
Review
Influenza A virus (IAV) is widely disseminated across different species and can cause recurrent epidemics and severe pandemics in humans. During infection, IAV attaches to receptors that are predominantly located in cell membrane regions known as lipid rafts, which are highly enriched in cholesterol and sphingolipids. Following IAV entry into the host cell, uncoating, transcription, and replication of the viral genome occur, after which newly synthesized viral proteins and genomes are delivered to lipid rafts for assembly prior to viral budding from the cell. Moreover, during budding, IAV acquires an envelope with embedded cholesterol from the host cell membrane, and it is known that decreased cholesterol levels on IAV virions reduce infectivity. Statins are commonly used to inhibit cholesterol synthesis for preventing cardiovascular diseases, and several studies have investigated whether such inhibition can block IAV infection and propagation, as well as modulate the host immune response to IAV. Taken together, current research suggests that there may be a role for statins in countering IAV infections and modulating the host immune response to prevent or mitigate cytokine storms, and further investigation into this is warranted.
Topics: Cholesterol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Influenza A virus; Influenza, Human; Membrane Microdomains; Sphingolipids; Viral Proteins; Virus Replication
PubMed: 36177026
DOI: 10.3389/fimmu.2022.982264 -
Virulence Dec 2023is an emerging spore-forming anaerobe that is often observed in -associated inflammatory bowel disease (IBD) exacerbations. Unlike , neither produces toxins nor...
is an emerging spore-forming anaerobe that is often observed in -associated inflammatory bowel disease (IBD) exacerbations. Unlike , neither produces toxins nor possesses toxin-encoding genetic loci, but is commonly found in both intestinal and extra-intestinal infections. Membrane lipid rafts are composed of dynamic assemblies of cholesterol and sphingolipids, allowing bacteria to gain access to cells. However, the direct interaction between and lipid rafts that confers bacteria the ability to disrupt the intestinal barrier and induce pathogenesis remains unclear. In this study, we investigated the associations among nucleotide-binding oligomerization domain containing 2 (NOD2), lipid rafts, and cytotoxicity in -infected gut epithelial cells. Our results revealed that lipid rafts were involved in -induced NOD2 expression and nuclear factor (NF)-κB activation, triggering an inflammatory response. Reducing cholesterol by simvastatin significantly dampened -induced cell death, indicating that the -induced pathogenicity of cells was lipid raft-dependent. These results demonstrate that NOD2 mobilization into membrane rafts in response to -induced cytotoxicity results in aggravated pathogenicity.
Topics: Clostridioides difficile; Clostridium; NF-kappa B; Membrane Microdomains; Cholesterol
PubMed: 37798913
DOI: 10.1080/21505594.2023.2265048 -
Cellular and Molecular Life Sciences :... Jan 2020Plasma membranes are heterogeneous and laterally compartmentalized into distinct microdomains. These membrane microdomains consist of special lipids and proteins and are... (Review)
Review
Plasma membranes are heterogeneous and laterally compartmentalized into distinct microdomains. These membrane microdomains consist of special lipids and proteins and are thought to act as signaling platforms. In plants, membrane microdomains have been detected by super-resolution microscopy, and there is evidence that they play roles in several biological processes. Here, we review current knowledge about the lipid and protein components of membrane microdomains. Furthermore, we summarize the dynamics of membrane microdomains in response to different stimuli. We also explore the biological functions associated with membrane microdomains as signal integration hubs. Finally, we outline challenges and questions for further studies.
Topics: Animals; Cell Membrane; Humans; Membrane Lipids; Membrane Microdomains; Plant Cells; Signal Transduction
PubMed: 31422442
DOI: 10.1007/s00018-019-03270-7 -
Microbial Biotechnology May 2022A form of lateral membrane compartmentalization in bacteria is represented by functional membrane microdomains (FMMs). FMMs are important for various cellular processes...
A form of lateral membrane compartmentalization in bacteria is represented by functional membrane microdomains (FMMs). FMMs are important for various cellular processes and offer application possibilities in microbial biotechnology. We designed a lipidomics method to directly measure relative abundances of lipids in detergent-resistant and detergent-sensitive membrane fractions of the model bacterium Bacillus subtilis 168 and the biotechnologically attractive miniBacillus PG10 strain. Our study supports previous work suggesting that cardiolipin and prenol lipids are enriched in FMMs of B. subtilis. Additionally, structural analysis of acyl chains of major phospholipids indicated that FMMs display increased order and thickness compared with the surrounding bilayer. Despite the 36% genome reduction, membrane and FMM integrity are largely preserved in miniBacillus PG10, as supported by analysis of membrane fluidity, flotillin distribution and gene expression data. The novel insights in FMM architecture reported here will contribute to further explore the biological significance of FMMs and the means by which FMMs can be exploited as heterologous production platforms. Moreover, our lipidomics method enables comparative FMM lipid profiling between different bacteria.
Topics: Bacillus subtilis; Detergents; Membrane Fluidity; Membrane Microdomains
PubMed: 34856064
DOI: 10.1111/1751-7915.13978 -
International Journal of Molecular... Aug 2019Recent findings have revealed the role of membrane traffic in the signaling of transforming growth factor-β (TGF-β). These findings originate from the pivotal function... (Review)
Review
Recent findings have revealed the role of membrane traffic in the signaling of transforming growth factor-β (TGF-β). These findings originate from the pivotal function of TGF-β in development, cell proliferation, tumor metastasis, and many other processes essential in malignancy. Actin and unconventional myosin have crucial roles in subcellular trafficking of receptors; research has also revealed a growing number of unconventional myosins that have crucial roles in TGF-β signaling. Unconventional myosins modulate the spatial organization of endocytic trafficking and tether membranes or transport them along the actin cytoskeletons. Current models do not fully explain how membrane traffic forms a bridge between TGF-β and the downstream effectors that produce its functional responsiveness, such as cell migration. In this review, we present a brief overview of the current knowledge of the TGF-β signaling pathway and the molecular components that comprise the core pathway as follows: ligands, receptors, and Smad mediators. Second, we highlight key role(s) of myosin motor-mediated protein trafficking and membrane domain segregation in the modulation of the TGF-β signaling pathway. Finally, we review future challenges and provide future prospects in this field.
Topics: Animals; Clathrin-Coated Vesicles; Endocytosis; Humans; Membrane Microdomains; Myosins; Protein Transport; Signal Transduction; Transforming Growth Factor beta
PubMed: 31408934
DOI: 10.3390/ijms20163913 -
Plant Physiology Apr 2020Plasma membranes provide a highly selective environment for a large number of transmembrane and membrane-associated proteins. Whereas lateral movement of proteins in... (Review)
Review
Plasma membranes provide a highly selective environment for a large number of transmembrane and membrane-associated proteins. Whereas lateral movement of proteins in this lipid bilayer is possible, it is rather limited in turgid and cell wall-shielded plant cells. However, membrane-resident signaling processes occur on subsecond scales that cannot be explained by simple diffusion models. Accordingly, several receptors and other membrane-associated proteins are organized and functional in membrane nanodomains. Although the general presence of membrane nanodomains has become widely accepted as fact, fundamental functional aspects, the roles of individual lipid species and their interplay with proteins, and aspects of nanodomain maintenance and persistence remain poorly understood. Here, we review the current knowledge of nanodomain organization and function, with a particular focus on signaling processes involving proteins, lipids, and their interactions. Furthermore, we propose new and hypothetical aspects of plant membrane biology that we consider important for future research.
Topics: Cell Membrane; Membrane Microdomains; Models, Biological; Proteolipids; Signal Transduction
PubMed: 31857424
DOI: 10.1104/pp.19.01349 -
International Journal of Molecular... Jul 2023This paper deals with the problems encountered in the study of eukaryotic cell membranes. A discussion on the structure and composition of membranes, lateral... (Review)
Review
This paper deals with the problems encountered in the study of eukaryotic cell membranes. A discussion on the structure and composition of membranes, lateral heterogeneity of membranes, lipid raft formation, and involvement of actin and cytoskeleton networks in the maintenance of membrane structure is included. Modern methods for the study of membranes and their constituent domains are discussed. Various simplified models of biomembranes and lipid rafts are presented. Computer modelling is considered as one of the most important methods. This is stated that from the study of the plasma membrane structure, it is desirable to proceed to the diverse membranes of all organelles of the cell. The qualitative composition and molar content of individual classes of polar lipids, free sterols and proteins in each of these membranes must be considered. A program to create an open access electronic database including results obtained from the membrane modelling of individual cell organelles and the key sites of the membranes, as well as models of individual molecules composing the membranes, has been proposed.
Topics: Eukaryotic Cells; Cholesterol; Cell Membrane; Sterols; Membrane Microdomains; Computer Simulation
PubMed: 37446404
DOI: 10.3390/ijms241311226 -
Cell Research Feb 2022The lateral segregation of membrane constituents into functional microdomains, conceptually known as lipid raft, is a universal organization principle for cellular...
The lateral segregation of membrane constituents into functional microdomains, conceptually known as lipid raft, is a universal organization principle for cellular membranes in both prokaryotes and eukaryotes. The widespread Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) family proteins are enriched in functional membrane microdomains at various subcellular locations, and therefore were hypothesized to play a scaffolding role in microdomain formation. In addition, many SPFH proteins are also implicated in highly specific processes occurring on the membrane. However, none of these functions is understood at the molecular level. Here we report the structure of a supramolecular complex that is isolated from bacterial membrane microdomains and contains two SPFH proteins (HflK and HflC) and a membrane-anchored AAA+ protease FtsH. HflK and HflC form a circular 24-mer assembly, featuring a laterally segregated membrane microdomain (20 nm in diameter) bordered by transmembrane domains of HflK/C and a completely sealed periplasmic vault. Four FtsH hexamers are embedded inside this microdomain through interactions with the inner surface of the vault. These observations provide a mechanistic explanation for the role of HflK/C and their mitochondrial homologs prohibitins in regulating membrane-bound AAA+ proteases, and suggest a general model for the organization and functionalization of membrane microdomains by SPFH proteins.
Topics: Bacteria; Membrane Microdomains
PubMed: 34975153
DOI: 10.1038/s41422-021-00598-3 -
International Journal of Molecular... Sep 2021Lipid model membranes are important tools in the study of biophysical processes such as lipid self-assembly and lipid-lipid interactions in cell membranes. The use of... (Review)
Review
Lipid model membranes are important tools in the study of biophysical processes such as lipid self-assembly and lipid-lipid interactions in cell membranes. The use of model systems to adequate and modulate complexity helps in the understanding of many events that occur in cellular membranes, that exhibit a wide variety of components, including lipids of different subfamilies (e.g., phospholipids, sphingolipids, sterols…), in addition to proteins and sugars. The capacity of lipids to segregate by themselves into different phases at the nanoscale (nanodomains) is an intriguing feature that is yet to be fully characterized in vivo due to the proposed transient nature of these domains in living systems. Model lipid membranes, instead, have the advantage of (usually) greater phase stability, together with the possibility of fully controlling the system lipid composition. Atomic force microscopy (AFM) is a powerful tool to detect the presence of meso- and nanodomains in a lipid membrane. It also allows the direct quantification of nanomechanical resistance in each phase present. In this review, we explore the main kinds of lipid assemblies used as model membranes and describe AFM experiments on model membranes. In addition, we discuss how these assemblies have extended our knowledge of membrane biophysics over the last two decades, particularly in issues related to the variability of different model membranes and the impact of supports/cytoskeleton on lipid behavior, such as segregated domain size or bilayer leaflet uncoupling.
Topics: Biophysics; Cell Membrane; Cytoskeleton; Lipid Bilayers; Lipids; Membrane Lipids; Membrane Microdomains; Microscopy, Atomic Force; Phospholipids; Sphingolipids
PubMed: 34576248
DOI: 10.3390/ijms221810085 -
Cancer Metastasis Reviews Jun 2020Changes in glycosylation on proteins or lipids are one of the hallmarks of tumorigenesis. In many cases, it is still not understood how glycan information is translated... (Review)
Review
Changes in glycosylation on proteins or lipids are one of the hallmarks of tumorigenesis. In many cases, it is still not understood how glycan information is translated into biological function. In this review, we discuss at the example of specific cancer-related glycoproteins how their endocytic uptake into eukaryotic cells is tuned by carbohydrate modifications. For this, we not only focus on overall uptake rates, but also illustrate how different uptake processes-dependent or not on the conventional clathrin machinery-are used under given glycosylation conditions. Furthermore, we discuss the role of certain sugar-binding proteins, termed galectins, to tune glycoprotein uptake by inducing their crosslinking into lattices, or by co-clustering them with glycolipids into raft-type membrane nanodomains from which the so-called clathrin-independent carriers (CLICs) are formed for glycoprotein internalization into cells. The latter process has been termed glycolipid-lectin (GL-Lect) hypothesis, which operates in a complementary manner to the clathrin pathway and galectin lattices.
Topics: Animals; Endocytosis; Galectins; Glycolipids; Glycoproteins; Glycosylation; Humans; Membrane Microdomains; Neoplasms; Shiga Toxin
PubMed: 32388640
DOI: 10.1007/s10555-020-09880-z